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Cryo-EM reveals that the autoinhibited neurofibromin dimer forms a large loop-shaped scaffold, which provides a molecular explanation for the extreme sensitivity of the NF1 gene to loss-of-function mutations in disease.
As 2021 comes to an end, we take this opportunity to look back through the pages of Nature Structural & Molecular Biology and consider some of the year’s highlights.
Transcription of eukaryotic protein-coding genes involves co-activator complexes, including TFIID and SAGA. A new study has determined the first high-resolution cryo-EM structure of the human SAGA complex, and has implications for defining SAGA function during multiple stages of eukaryotic transcription.
New work from Guberovic et al. sheds light on the evolution of the histone variant macroH2A1.1 and its relationship with the NAD+-using poly(ADP-ribose) polymerase PARP1. Their study shows that macroH2A1.1 has been a nuclear regulator of NAD+ flux as far back evolutionarily as pre-metazoan protists, but has been loosening the reins on PARP1, thus expanding PARP1’s cellular roles.
How p97 processes diverse clients has remained controversial. van den Boom, Kueck and colleagues now demonstrate that p97 recognizes an internal segment of the PP1 partner I3 and then threads an I3 peptide loop through the channel in p97 to strip I3 off PP1.
Structures of antifungal AmB ‘sponges’ are illuminated by high-resolution SSNMR. These AmB assemblies consist of asymmetric head-to-tail homodimers staggered in a clathrate-like lattice with large void volumes similar to the size of sterols.
Cryo-EM and three-dimensional variability analyses reveal the structure of the autoinhibited 640-kDa NF1 dimer, providing a long-sought-after molecular explanation for the extreme sensitivity of the NF1 gene to loss-of function mutation in disease.
The cryo-EM structure of the human SAGA coactivator complex reveals high-resolution details of the core and TRRAP modules, providing insights on a metazoan-specific architecture and the structural basis for incorporation of the splicing module in mammalian cells.
Here the authors structurally investigate elongating human RNA polymerase I at 2.7 Å using cryo-electron microscopy, as well as an RNA polymerase I open complex at 3.3 Å and bound to initiation factor RRN3 at 3.2 Å.
MacroH2A histone variants originated before the split of fungi and animals. ADP-ribose binding is an ancestral feature of their macrodomains and is linked to the compartmental regulation of NAD metabolism. This function was selected for during the evolution of metazoans.
Genetic and genomic analyses show that S. cerevisiae DNA polymerase δ extrinsically proofreads for errors by polymerase ε and itself, and demonstrate that the symmetry of replication fidelity is achieved via coordinated efforts of intrinsic and extrinsic proofreading and DNA mismatch repair.
Cryo-EM structures of the cytosolic metazoan GET complex, which targets nascent tail-anchored membrane proteins to the endoplasmic reticulum, reveal interactions that coordinate client transfer between two protein chaperones.
The discovery that mRNA degradation and deadenylation are uncoupled during meiosis in budding yeast provides a unique context to examine the regulation of each process individually, and reveals that transcript length is a determinant of deadenylation rates across eukaryotes.